Medicine and Health Sciences Commons^™

Multicenter, Double-Blind, Placebo-Controlled Trial Of Seviprotimut-L Polyvalent Melanoma Vaccine In Patients With Post-Resection Melanoma At High Risk Of Recurrence, Craig L Slingluff, Karl D Lewis, Robert Andtbacka, John Hyngstrom, Mohammed Milhem, Svetomir N Markovic, Tawnya Bowles, Omid Hamid, Leonel Hernandez-Aya, Joel Claveau, Sekwon Jang, Prejesh Philips, Shernan G Holtan, Montaser F Shaheen, Brendan Curti, William Schmidt, Marcus O Butler, Juan Paramo, Jose Lutzky, Arvinda Padmanabhan, Sajeve Thomas, Daniel Milton, Andrew Pecora, Takami Sato, Eddy Hsueh, Suprith Badarinath, John Keech, Sujith Kalmadi, Pallavi Kumar, Robert Weber, Edward Levine, Adam Berger, Anna Bar, J Thaddeus Beck, Jeffrey B Travers, Catalin Mihalcioiu, Brian Gastman, Peter Beitsch, Suthee Rapisuwon, John Glaspy, Edward C Mccarron, Vinay Gupta, Deepti Behl, Brent Blumenstein, Joanna J Peterkin

Department of Medical Oncology Faculty Papers

Background: Most patients with advanced melanomas relapse after checkpoint blockade therapy. Thus, immunotherapies are needed that can be applied safely early, in the adjuvant setting. Seviprotimut-L is a vaccine containing human melanoma antigens, plus alum. To assess the efficacy of seviprotimut-L, the Melanoma Antigen Vaccine Immunotherapy Study (MAVIS) was initiated as a three-part multicenter, double-blind, placebo-controlled phase III trial. Results from part B1 are reported here.

Methods: Patients with AJCC V.7 stage IIB-III cutaneous melanoma after resection were randomized 2:1, with stage stratification (IIB/C, IIIA, IIIB/C), to seviprotimut-L 40 mcg or placebo. Recurrence-free survival (RFS) was the primary endpoint. For …

Dark Side Of Cancer Therapy: Cancer Treatment-Induced Cardiopulmonary Inflammation, Fibrosis, And Immune Modulation, Boopathi Ettickan, Chellappagounder Thangavel

Department of Dermatology and Cutaneous Biology Faculty Papers

Advancements in cancer therapy increased the cancer free survival rates and reduced the malignant related deaths. Therapeutic options for patients with thoracic cancers include surgical intervention and the application of chemotherapy with ionizing radiation. Despite these advances, cancer therapy-related cardiopulmonary dysfunction (CTRCPD) is one of the most undesirable side effects of cancer therapy and leads to limitations to cancer treatment. Chemoradiation therapy or immunotherapy promote acute and chronic cardiopulmonary damage by inducing reactive oxygen species, DNA damage, inflammation, fibrosis, deregulation of cellular immunity, cardiopulmonary failure, and non-malignant related deaths among cancer-free patients who received cancer therapy. CTRCPD is a complex …

Efficient Killing Of Tumor Cells By Car-T Cells Requires Greater Number Of Engaged Cars Than Tcrs, Nadia Anikeeva, Sergey Panteleev, Nicholas W Mazzanti, Mizue Terai, Takami Sato, Yuri Sykulev

Department of Microbiology and Immunology Faculty Papers

Although CAR-T cells are widely used to treat cancer, efficiency of CAR-T cell cytolytic responses has not been carefully examined. We engineered CAR specific for HMW-MAA (highmolecular- weight melanoma-associated antigen) and evaluated potency of CD8+ CAR-T cells to release cytolytic granules and to kill tissue-derived melanoma cells, which express different levels of HMW-MAA. CAR-T cells efficiently killed melanoma cells expressing high level of HMW-MAA, but not melanoma cells with lower levels of HMW-MAA. The same melanoma cells presenting significantly lower level of stimulatory peptide- MHC ligand were readily lysed by T cells transduced with genes encoding α,β-TCR specific for the …

Phase 1 Study Of Safety, Tolerability And Immunogenicity Of The Human Telomerase (Htert)-Encoded Dna Plasmids Ino-1400 And Ino-1401 With Or Without Il-12 Dna Plasmid Ino-9012 In Adult Patients With Solid Tumors, Robert H Vonderheide, Kimberly A Kraynyak, Anthony F Shields, Autumn J Mcree, Jennifer Johnson, Weijing Sun, Ashish V Chintakuntlawar, Jan Pawlicki, Albert J Sylvester, Trevor Mcmullan, Robert Samuels, Joseph J Kim, David Weiner, Jean D Boyer, Matthew P Morrow, Laurent Humeau, Jeffrey M Skolnik

Department of Medical Oncology Faculty Papers

BACKGROUND: Human telomerase reverse transcriptase (hTERT) is frequently classified as a 'universal' tumor associated antigen due to its expression in a vast number of cancers. We evaluated plasmid DNA-encoded hTERT as an immunotherapy across nine cancer types.

METHODS: A phase 1 clinical trial was conducted in adult patients with no evidence of disease following definitive surgery and standard therapy, who were at high risk of relapse. Plasmid DNA encoding one of two hTERT variants (INO-1400 or INO-1401) with or without plasmid DNA encoding interleukin 12 (IL-12) (INO-9012) was delivered intramuscularly concurrent with the application of the CELLECTRA constant-current electroporation device …

Glioma Stem Cells As Immunotherapeutic Targets: Advancements And Challenges, Keenan Piper, Lisa Depledge, Michael Karsy, Charles Cobbs

Department of Neurosurgery Faculty Papers

Glioblastoma is the most common and lethal primary brain malignancy. Despite major investments in research into glioblastoma biology and drug development, treatment remains limited and survival has not substantially improved beyond 1–2 years. Cancer stem cells (CSC) or glioma stem cells (GSC) refer to a population of tumor originating cells capable of self-renewal and differentiation. While controversial and challenging to study, evidence suggests that GCSs may result in glioblastoma tumor recurrence and resistance to treatment. Multiple treatment strategies have been suggested at targeting GCSs, including immunotherapy, posttranscriptional regulation, modulation of the tumor microenvironment, and epigenetic modulation. In this review, we …

Combined High-Dose Lattice Radiation Therapy And Immune Checkpoint Blockade For Advanced Bulky Tumors: The Concept And A Case Report, Liuqing Jiang, Xiaobo Li, Jianping Zhang, Wenyao Li, Fangfen Dong, Cheng Chen, Qingliang Lin, Chonglin Zhang, Fen Zheng, Weisi Yan, Yi Zheng, Xiaodong Wu, Benhua Xu

Department of Radiation Oncology Faculty Papers

Although the combination of immune checkpoint blockades with high dose of radiation has indicated the potential of co-stimulatory effects, consistent clinical outcome has been yet to be demonstrated. Bulky tumors present challenges for radiation treatment to achieve high rate of tumor control due to large tumor sizes and normal tissue toxicities. As an alternative, spatially fractionated radiotherapy (SFRT) technique has been applied, in the forms of GRID or LATTICE radiation therapy (LRT), to safely treat bulky tumors. When used alone in a single or a few fractions, GRID or LRT can be best classified as palliative or tumor de-bulking treatments. …